The overall objective of this research is to study the mechanisms governing the interactions between the brain and the immune system. Using a number of different approaches to perturb the central nervous system of animals, we will examine subsequent alterations in in vivo and in vitro specific immune responsiveness. Particular attention will be given to the effects of these perturbations on lymphocyte (B-cell T-helper and T-suppressor) and macrophage function and their interactions. The effect of electrolytic cerebral lesions on the ability of trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) primed animal to respond in vitro to this antigen will be studied with emphasis on T and B-cell function. Similar types of experiments are planned to define the effect of chemical lesions induced by intracisternal injection of 6-hydroxydopamine (6-OHDA). In animals treated with 6-OHDA the in vivo primary antibody response to thymic dependent (TD) and independent antigens (TI) will be assessed. The ability of antigen specific B-cells obtained from 6-OHDA treated animals to respond in vitro to a TI antigen and to a TD antigen in the presence of T-helper cells will be studied. Additionally, antigen presentation by splenic adherent cells obtained from these treated animals will be determined as will the presence of increased suppressor cell activity (macrophage or T-suppressor cell). We have demonstrated that serotonin can modulate in vivo antibody responsiveness and that lymphy and macrophages have serotonin receptors. Experiments are planned to further investigate the mechanisms of serotonin induced modulation of the antibody response in vivo and in vitro. The same immunologic approach as described for 6-OHDA treated animals will be employed. Further characterization of lymphocytes with serotonin receptors is planned together with experiments to define the functional significance of serotonin receptors on these lymphocytes as well as macrophages. A series of experiments to define the effects of chemical (6-OHDA) and electrolytic lesions on lymphoid tissue monoamine levels employing high pressure liquid chromatograph (HPLC) are planned. Lastly, we propose to ivestigate the temporal effect of an immunogenic and tolerogenic antigen challenge on hypothalamic monoamine levels employing HPLC.